Microbiologie/Virologie

GR 122222X is an inhibitor of topoisomerase II.

Artefenomel (OZ439) is an orally active anti-malarial ozone analog with antiviral activity for the study of SARS-CoV-2 infections and malaria infections.

Nikkomycin Z (Nikkomycin Z from Streptomyces tendae) is a competitive chitin synthase inhibitor.It inhibitor of the growth of filamentous fungi, insects,

CTSL/CAPN1-IN-2 (Compound 14b) serves as an orally active inhibitor targeting both CTSL and CAPN1, manifesting IC50 values of 6.88 nM for CTSL and 347.6 nM for CAPN1 respectively. This compound not only displays anti-inflammatory attributes but also features favorable pharmacokinetic properties. Moreover, CTSL/CAPN1-IN-2 shows extensive antiviral effects against coronaviruses by inhibiting viral entry [1].

Neuraminidase-IN-18 (compound N5), a novel polyheterocyclic neuraminidase (NA) inhibitor, demonstrates significant inhibitory activity against H5N1 NA, with an IC 50 of 0.14 μM against the wild-type H5N1 NA and 0.27 μM against the H5N1-H274Y mutant NA. This compound effectively binds to NAs, inhibiting influenza virus replication at the cellular level [1].

N-Cbz-L-Cysteine (Cbz-cysteine) (compound 5) functions as a potent inhibitor of β-lactamase II, exhibiting a K i value of 97 µM [1].

BDM91288, an orally active AcrB efflux pump inhibitor of pyridinium piperazine, enhances the in vivo efficacy of levofloxacin in treating Klebsiella pneumoniae pulmonary infection in mouse models [1].

Antibacterialagent 278 (compound B1) is an antimicrobial agent that exhibits potent inhibitory activity against Gram-positive bacteria.

Antifungal agent 100 (compound 3i) demonstrates notable antifungal activity, exhibiting an EC 50 of 0.33 mg/L against S. sclerotiorum. It also possesses an IC 50 value of 0.63 mg/mL targeting the Succinate dehydrogenase (SDH) of the same organism [1].

<p>HBV/HDV-IN-3 (Compd 1) acts as a dual inhibitor for HBV and HDV, demonstrating an efficacy (EC 50) below 50 nM against HBV .</p>

Antibacterial Agent 172 (Compound 6a), a <i>Clostridioides difficile (Cd) SpoVD inhibitor with an IC50 value of 89 nM, effectively inhibits the sporulation of Clostridioides difficile. It is useful for research on bacterial infections [1].

Compound 174 (Compound 5g), an antibacterial agent, exhibits potent anti-infective properties in vivo along with appreciable pharmacokinetic profiles. This highly active substance demonstrates favorable biofilm removal capabilities, low hemolysis, and acceptable mammalian cell toxicity [1].

LpxA-IN-1, a novel UDP-N-acetylglucosamine acyltransferase (LpxA) inhibitor exhibiting potent activity (IC 50 2 nM), effectively targets Pseudomonas aeruginosa

SAG-524 is a powerful oral small molecule that inhibits HBV viral replication. In HepG2.2.15 cells, SAG-524 reduced HBV-DNA and HbsAg levels in the supernatant with IC₅₀ values of 0.92 nM and 1.4 nM, respectively [1].

Metallo-β-lactamase-IN-14 (Compound 17e) serves as an inhibitor of Metallo-β-Lactamase, displaying inhibitory activity against VIM-1 and VIM-2. This compound also exhibits antibacterial effects on Gram-negative (GN) bacteria and P. aeruginosa [1].

HIV-1 inhibitor-14: potent, broad HIV-1 RT inhibitor. IC50=0.14μM. Effective against wild-type and resistant strains, EC50=5.79-28.3nM.

N'-(2-Fluorophenyl)pyrazine-2-carbohydrazide is a Ole1p desaturase inhibitor as well as antifungal agent [1].

Elongation factor P-IN-2, a β-lysine derivative, is a potent EFP inhibitor reducing E. coli growth.

DENV-IN-6, a potent anti-DENV (I-IV) and HIV-1 IIIB inhibitor with EC50 ranging 6.8-17.5 μM for DENV and EC50 0.0181 μM for HIV-1.

SMCypIC31, a non-peptide cyclophilin inhibitor, blocks PPIase at 0.1 μM IC50 and fights various HCV genotypes (EC50: 1.20-7.76 μM).

TAN-1057C is a potent antibiotic with antimicrobial activity against both Gram-negative and Gram-positive bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA).

Antifungal agent 27 shows moderate action against MRSA, weak against C. albicans, with MICs of 8 μg/mL and 32 μg/mL, respectively.

Rubropunctatin is a monascus pigment with very potent cancer cell proliferation inhibitory effects.

RmlA-IN-2: Strong RmlA blocker, hinders l-rhamnose synthesis & alters bacterial wall permeability (IC50: 0.303 μM).

Anti-MRSA agent 3 targets MRSA with 0.098 μg/ml MIC, low toxicity, binds DNA, and disrupts cell walls/membranes.

RAD51-IN-6, a potent RAD51 gene inhibitor, may help research mitochondrial disorders. (WO2021164746A1, cmpd 23)

20S Proteasome-IN-4: brain-penetrant, parasite-specific, oral, inhibits T.b. brucei proteasome (IC50: 6.3nM), for HAT research.

LasR-IN-2 blocks LasR via H-bond with TRY-56, useful in bacterial infection and CF research.

9-tert-Butyldoxycycline exhibits immunomodulatory activity by altering the polarization state of polymorphonuclear neutrophils and ameliorating inflammatory responses in ischemia-reperfusion injury models. Additionally, 9-tert-Butyldoxycycline serves as a ligand for the "Tet-On" inducible gene expression system.

Fenbenicillin (Phenbenicillin) potassium is a semi-synthetic penicillin with antibacterial spectrum activity.

Imidocarb dihydrochloride monohydrate is an effective antiprotozoal agent against the parasite B. bovis (IC50: 87 μg/ml).

TLR8 agonist 4 inhibits wild-type and lamivudine/entecavir-resistant HBV; IC50: 0.15 μM and 0.10 μM.

RCB18350 is an antituberculosis agent and an isoxazole derivative. It demonstrates bacteriostatic properties by inhibiting the growth of Mycobacterium tuberculosis, with a minimum inhibitory concentration (MIC) of 1.25 μg/mL. RCB18350 is effective against multi-drug resistant Mycobacterium tuberculosis (MDR-TB) clinical isolates, Mycobacterium bovis BCG, and Mycobacterium avium, all of which are slow-growing mycobacteria.

HIV-1 inhibitor-18 blocks HIV-1 capsid, acts on NL4-3 strain (EC50: 2.57 μM), has low cytotoxicity (MT-4 CC50: >8.55).

Methyl piperazine-2-carboxylate (compound 4) is a potent activator of METTL3/METTL14/WTAP. It enhances the production of HIV-1p24 viral particles and increases the level of N6-methyladenosine in the viral RNA genome.

HBV-IN-11 is a potent inhibitor of HBsAg secretion (EC50: 0.46 μM).

BM635 hydrochloride, an MmpL3 inhibitor, strongly blocks Divergent bacteriophage H37Rv (MIC50: 0.08 μM), with doubled in vivo potency.

NBD-14189: Potent HIV-1 entry blocker, binds gp120, IC50: 89 nM, strong antiviral (EC50 <200 nM).

Antitumor agent-74, a quinazoline derivative, inhibits DNA, arrests cell cycle, and induces apoptosis with agent-75.

<p>SARS-CoV-2-IN-22 is a SARS-CoV-2 pseudovirus inhibitor (IC50: 16.96 μM).</p>

BRD-K98645985: BAF inhibitor, binds ARID1A, reverses HIV-1 latency, EC50 ~2.37μM, alters nucleosome placement.

ZK-316 is a potent and broad-spectrum NNRTI inhibitor with an EC50 range of 0.99 to 75.1 nM. It is applicable for HIV research.

NBTIs-IN-5 inhibits Mycobacterium abscessus DNA with IC50 1.5μM, halts growth at MIC90 0.4μM.

NITD-688 is a pan-serotype inhibitor targeting the dengue virus NS4B protein, effective through oral administration.

Antifungalagent 127 (Compound 6c) is an antifungal agent with potent inhibitory activity against Botrytis cinerea and Rhizoctonia solani.

XR8-89, a potent PLpro inhibitor (IC50=0.1μM), blocks SARS-CoV-2 replication; useful for research.

<p>ZLM-66: Doravirine analog, HIV-1 NNRTI inhibitor, IC50: 41nM, EC50: HIV-1 13nM, cIAP1 0.32nM; useful in AIDS research.</p>

Emtricitabine triphosphate is an active metabolite of Emtricitabine, a drug for HIV/HBV that inhibits reverse transcriptase.

FtsZ-IN-13 (Compound C11) functions as an inhibitor of the temperature-sensitive mutant Z (FtsZ), exhibiting IC50 values of 47.97 μM for FtsZSa and 34 μM for FtsZPa. It demonstrates notable antibacterial activity against Staphylococcus aureus (with a minimum inhibitory concentration of 2 μg/mL), cystic fibrosis Staphylococcus aureus clinical isolates, and methicillin-resistant Staphylococcus aureus (MRSA). FtsZ-IN-13 is applicable in research on antibiotic resistance.

(E)-2,6-Di-tert-butyl-4-(4-(diethylamino)styryl)pyrylium TFA (Compound 4a) functions as a Gram-negative outer membrane permeabilizer by targeting Met47 in LptA to disrupt LptA/LptC interactions, exhibiting synergistic antibacterial activity. This compound, when in the form of (trifluoromethanesulfonate), enhances the efficacy of pol B against both wild-type and multi-drug resistant A. baumannii and E. coli strains. Additionally, (E)-2,6-Di-tert-butyl-4-(4-(diethylamino)styryl)pyrylium (trifluoromethanesulfonate) serves as an adjuvant for antibiotics combating multi-drug resistant Gram-negative bacteria.

HIV-1 inhibitor-52: potent, broad-spectrum with EC50s 1.6-6.4 nM against various HIV-1 strains.

Dioxidine is an antimicrobial agent that can inhibit bacterial growth. It is utilized in research on pyogenic infections.

"Plm IV inhibitor-2: Potent for Plm IV (IC50=24nM), affects Plm II/Plm I; malaria research compound."

<p>(Z)-Lanoconazole, an imidazole antifungal for dermatophytosis and onychomycosis, inhibits fungal ergosterol production.</p>

QPX7728 is an of ultra-broad-spectrum boronic acid beta-lactamase.

GSK-2878175, a NS5B inhibitor, is used potentially for the treatment of HCV infection.

ZIKV-IN-5 is an acid-stable, low cytotoxic anti-ZIKV agent with an EC50 value of 0.71 μM. ZIKV-IN-5 showed effective inhibition of ZIKV NS5 MTase activity.

Adafosbuvir has antiviral activity.

Cap-dependent endonuclease-IN-6 (compound 13) is a Cap-dependent endonuclease (CEN) inhibitor that inhibits influenza virus.

Gln-AMS (TFA) is a type Ia amido-tRNA synthetase (AARS) inhibitor with a Ki value of 1.32 μM for glutaminyl-tRNA synthetase.

RAD51-IN-5 blocks RAD51; may aid mitochondrial disorder research. (WO2021164746A1, cmpd 3)

<p>AK-968-11563024 is an inhibitor targeting marine V. vulnificus NAT [(VIBVN)NAT] with an IC50 value of 18.86 µM. In V. vulnificus, NAT (aromatic amine N-acetyltransferase) plays a role in drug metabolism, contributing to drug resistance. Thus, AK-968-11563024 can be used for research related to drug tolerance.</p>

AnCDA-IN-1 (Compound J075-4187) is an inhibitor of chitin deacetylase (CDA) exhibiting antifungal properties. It possesses an IC50 of 4.24 μM against A. nidulans AnCDA. The compound demonstrates a minimum inhibitory concentration (MIC) of 260 μg/mL and a minimum fungicidal concentration (MFC) of 520 μg/mL for food spoilage fungi and plant pathogenic fungi. AnCDA-IN-1 is applicable for research in the antifungal domain.

Aurachin C is a quinoline alkaloid belonging to the isoprenoid class, known for its antimalarial, antifungal, and antibacterial properties. It acts as a selective terminal oxidase inhibitor.

(S)-Batylalcohol (1-O-Octadecyl-sn-glycerol) is an analogue of phosphonoformic acid (PFA) and demonstrates higher in vitro antiviral activity against human immunodeficiency virus type 1 (HIV-1) compared to PFA. This compound is applicable in antiretroviral research.

Menoctone is an orally effective antimalarial agent that inhibits blood-induced rodent malaria. It enhances the antimalarial effects of chloroquine or quinine, making it useful for malaria research.

Antibacterial agent 113 targets multiple bacteria including P. aeruginosa and E. coli, showing efficacy at MIC 15625 μM.

Faldaprevir is an orally effective, selective, non-covalent HCV NS3/4A protease inhibitor with high inhibitory activity against HCV 1a and 1b genotype.

Antimalarial agent 3 has a potent IC50 of 0.035 μM against Plasmodium and high selectivity for mammalian cells.

GT-055 (LCB18-055) is a novel inhibitor of broad-spectrum β-lactamase.

Antileishmanial agent-4, a ribonucleoside analogue, targets L.infantum and T.cruzi with EC50s of 0.68 μM and 0.83 μM.

Cap-dependent endonuclease-IN-14 hinders CEN and could treat influenza virus infections. (Patent CN113620948A, compound 1-c).

Antileishmanial agent-4, a ribonucleoside analogue, functions as an antileishmanial agent [1].

Antitubercular agent-11 (Compound 1e) is an antitubercular agent with a bulkier electron-donating group (Bu-t) that shows the best MIC value of 0.060 μg/mL [1].

FWM-1 blocks SARS-CoV-2 NSP13, hinders ATP binding, with -328.6 kcal/mol binding energy.

Purine PRTase-IN-2 inhibits Pf, Pv, Tbr PRT; Ki: 30, 20, 2 nM.

Compound 25b inhibits DENV2/ZIKV NS2B/NS3 proteases; IC50: ZIKV 0.67μM, DENV2 4.38μM.

Neuraminidase-IN-4 inhibits neuraminidase (EC50: 1.59 μM) and has strong anti-H5N1 activity.

<p>TKB272 is an orally active antiviral agent that selectively targets the main protease (Mpro) of SARS-CoV-2, effectively inhibiting the infection and replication of various strains, including Omicron variants (such as XBB.1.5 and EG.5.1). It exhibits an enzyme inhibitory activity with an IC50 of 0.7 µM against SARS-CoV-2WK-521 Mpro and shows potent antiviral activity at the cellular level with an EC50 as low as 2.6 nM in HeLahACE2-TMPRSS2 cells against the BQ.1.1 strain. TKB272 also has a CC50 of 98 µM, indicating low cytotoxicity. Furthermore, it demonstrates a significant suppression of SARS-CoV-2XBB.1.5 replication in the B6.Cg-Tg(K18-hACE2)2-Prlmn/J transgenic mouse model, suggesting potential use in the research of SARS-CoV-2 infections.</p>

Antifungal agent 16 has antimicrobial activity comparable to that of ciprofloxacin and has higher antifungal activity than fluconazole.

Compound 18a: potent vs. T. brucei (IC50: 0.47 μM), >2x efficacy compared to Nifurtimox, good ADME, binds AT-rich DNA.

Alphavirus-IN-1 blocks VEEV (EC50: 0.24 μM) & EEEV (EC50: 0.16 μM), non-toxic, stable in mice plasma.

FIZ1 degrader 1 (compound 1) is an IMiD-based molecular glue degrader targeting FIZ1.

H2S scavenger 1 triflate (Compound 7b) serves as a selective H2S depleting agent, particularly against glutathione. This compound impedes the formation of bacterial biofilms and enhances the sensitivity of Staphylococcus aureus to gentamicin or photosensitizers by depleting H2S.

CYP51-IN-14 (compound 1n), a derivative of Fluconazole, functions as an effective antifungal agent. This compound inhibits Microsporum gypseum and Candida albicans with a minimum inhibitory concentration (MIC80) of 1 μg/mL.

Homer is a probe designed to target WD repeat domain 5 (WDR5). In MV4-11 cells, Homer induces the degradation of WDR5 with a half-maximal degradation concentration (DC50) of 53 nM. At a concentration of 1 µM, Homer decreases the protein levels of WDR5 in MV4-11 cells without affecting the mRNA levels that encode WDR5.

ART615 is a related isomer of ART558. ART615 inhibits Polθ by <10% at 12 μM and is able to act as a control for ART558 (IC50:7.9 nM).

HIV-1inhibitor-82 (Compound L14) is a small molecule inhibitor of HIV-1 entry with oral bioavailability, exhibiting an IC50 value of 0.39 μM. It holds potential for research in combating HIV-1 infection.

THU dihydrate, a potent CDA inhibitor, outperforms cytidine by blocking the enzyme's active site.

AVE-1330A sodium is a beta-Lactamase inhibitor.

PCNA-IN-1 (Compound 11) is an inhibitor of the PCNA/PIP-box interaction, with an IC50 greater than 50 μM. It is applicable in cancer research.

<p>ZG297 is an agonist of Staphylococcus aureus ClpP (SaClpP) with an EC50 of 0.26 μM. It degrades SaFtsZ and inhibits bacterial cell division, exhibiting antistaphylococcal activity by inhibiting S. aureus 8325-4 and MRSA strains, with a MIC range of 0.063-256 μg/mL. In mouse models, ZG297 demonstrates anti-infective properties.</p>

Anti-infective agent 10 (Compound Example 30) is an ns5b polymerase inhibitor that functions as an anti-HCV agent.

BRL-42715 is an effective inhibitor of bacterial beta-lactamases.

JTK-109 is an inhibitor of hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitor and inhibits G1b and G3a subgenomic replicons and recombinant enzymes.

Vaniprevir is a competitive HCV NS3/4A protease inhibitor, an antiviral(hepatitis C virus) drug that acts directly and blocks the viral replication process.

Cap-dependent endonuclease-IN-1: potent, oral inhibitor with antiviral properties against influenza.

Tigemonam is a monobactam, a novel orally administered monobactam that protects against gram-negative aerobic bacterial pathogens. Cost-effective and quality-assured.

Eravacycline dihydrochloride (TP-434-046) is a potent and broad-spectrum antibacterial agent against six E. coli (MICs: 0.125-0.25 mg/L).

HRO761 is a potent Werne r syndrome RecQ DNA deconjugase (WRN) inhibitor that can be used to study cancers such as colon and stomach cancer.